The incidence of bacterial infection caused by bacterial contamination of medical appliances has never been reduced to a satisfactory level. This is particularly true in connection with medical appliances which cannot normally be sterilized in autoclaves or which when in use encounter bacteria containing environments. For example, sutures, catheters, surgical tape, tubings, sponges, gloves, pads, surgical covers and certain medical instruments cannot be autoclaved to insure sterility but often must be used in areas where pathogenic bacteria are encountered. Accordingly, for such medical appliances, the art has long sought means and methods of rendering those medical appliances antibacterial and, hopefully, self-sterilizing. The general approach in the art has been that of coating the medical appliance, or a surface thereof, with a bacteriocide. However, since most bacteriocides are partly water soluble, or at least require sufficient solubilization for effective antibacterial action, simple coatings of the bacteriocides have been proven unreliable. For this reason, the art has further sought to incorporate the bacteriocides into the medical appliance or at least provide a stabilized coating thereon.
The art has taken many different directions in attempting to solve this problem, but finding the combination of effective bacteriocides and means of retaining that bacteriocide in or on the medical appliance has either eluded the art in regard to some applications, or the art has not found totally satisfactory solutions in regard to other applications. For example, many of the medical appliances which encounter the above noted problem are made of non-metallic materials, such as plastics, cat gut, and gelatin. Since these materials cannot be adequately autoclaved, at least in connection with the environment of use, these types of medical appliances present the problem in its most difficult form and the problem has never been solved. One of the earlier attempts to solve this problem is discussed in U.S. Pat. No. 1,006,854, wherein cat gut, for suture purposes, is treated with iodine to disinfect the suture material. However, since the iodine is not tightly bound to the cat gut it is rapidly released during use and quickly inactivated.
With the increased use of polymeric materials for construction of medical appliances, such as catheters, artificial blood vessels, injection tubing, surgical tape and the like, the problem of a self sterilizing polymer has become more important. The art, therefore, sought combinations of plastics and antibacterial agents wherein the antibacterial agent could be fixedly attached to or incorporated in the plastic so that the combination thereof could be used for the manufacture of these plastic medical appliances. This relatively recent effort in the art has taken a myriad of different approaches. For example, U.S. Pat. No. 3,401,005, discloses that a combination of polyvinylpyrrolidone and iodine could be applied to cotton gauze and the like and when dried would have a germicidal characteristic. In a similar effort, a combination of polyvinylpyrrolidone and iodine was placed in absorbable, gelatin foams to produce surgical sponges. It was also found that iodine could actually be complexed with polyvinylpyrrolidone and the complexed composition would slowly release iodine under use conditions. Solid polyvinylpyrrolidone complexed with iodine is disclosed in U.S. Pat. No. 3,898,326 as useful as a disinfectant material and U.S. Pat. No. 4,017,407 extends that composition to include other ingredients such as detergents.
Improved polyvinylpyrrolidone/iodine complexes are disclosed in U.S. Pat. No. 4,094,967, for coating dressing materials and the like, but the art has not been successful in using polyvinylpyrrolidone/iodine complex as a material of construction for producing medical appliances. U.S. Pat. No. 4,113,851, suggests complexing iodine with a preformed polymer of 2-pyrrolidone and then treating with an emulsion of a polyacrylic acid to impregnate the polyvinylpyrrolidone/iodine complex with the acid.
The lack of success of producing medical appliances with complexed polyvinylpyrrolidone and iodine led the art toward other approaches and U.S. Pat. No. 4,010,259 suggests complexing iodine with polysaccharide, such as starch, dextran or cellulose, but here again, these materials are not suitable for materials of construction of most medical appliances.
In yet another approach, U.S. Pat. No. 3,598,127 suggests infusing an antibacterial substance, such as neomycin and the like, into a polysiloxane rubber, while U.S. Pat. No. 4,186,745 suggests a similar approach with microporous polyethylene, polypropylene, or polyflurocarbon polymers. These approaches are merely mixtures and the bacteriocidal agent is not chemically combined to the plastic and slowly released.
In an approach somewhat similar to the above, antibiotics and germicides, e.g. penicillin and cetylpyridinium chloride, are infused into a hydrophilic polymer for coating medical appliances such as catheters, according to the disclosure of U.S. Pat. No. 3,566,874. Such antibiotic approaches have other limitations in that the antibiotic is not effective against all organisms.
In another approach, multifilament suture strands are impregnated with a water soluble antimicrobial agent, such as penicillin, and then coated with polyurethane polymer so as to maintain the antimicrobial agents. A similar approach is disclosed in U.S. Pat. No. 3,987,797, where a surgical suture is coated with a copolymer of polyquaternary polyurethane and a polyanionic polymer, such as heparin and then treated with an antimicrobial compound, such as penicillin. There have also been efforts to incorporate bacteriocides, in gross, in polymers simply by mixing with the polymer, and U.S. Pat. No. 2,947,282, is representative thereof.
Polyurethane would be most useful in producing medical appliances of the present nature, and efforts along the above lines have also been made to render those polyurethane appliances self-sterilizing. For example, U.S. Pat. No. 3,235,446, prepares a polyurethane foam by the reaction between a liquid polyfunctional hydroxyl terminated polyether or polyester and a liquid polyfunctional organic di-isocyanate, with subsequent exposure to water so that a foam results. The resulting plastic is a thermoset. The foam is then treated with an iodine solution. This approach is successful in producing a prefoamed polyurethane complexed with iodine, but materials prepared in this manner are not thereafter convertible into other medical appliances since they are not thermoplastic but thermosetting. Few or no medical devices are manufactured with thermosetting plastic resins. In addition, the diisocyanate used in the manufacture is a toxic substance and difficult to handle.
U.S. Pat. No. 3,897,797 relates specifically to thermosetting polyurethanes which are different from the thermoplastic polyurethanes which we have investigated. Shelenski, Mills and Levenson have chosen a special situation in thermosetting polyurethane resins by reacting isocyanetes with relatively high molecular weight (M.W. 1000) compounds having terminal hydroxal groups and containing not less than 30% ethylene oxide. Yet, short chain polyalcohols are often used in mixtures to provide for sparse cross-linking and these sparsely cross-linked compounds can be thermoplastic. Although such cross-linked thermoplastic resins have high tear resistance, steric hindrance renders the ##STR1## urethane linkages which complex with iodine inaccessible in highly cross-linked plastics. This factor may have discouraged the investigation of the possibility of complexing iodine onto thermoplastic polyurethanes which are only sparsely cross-linked.
As can thus be appreciated, considerable effort has been expended, yet success in the art has been elusive. This is particularly true in connection with the manufacture of medical appliances, such as catheters and the like which should not only be sterile, but have good tensile properties and yet be relatively inexpensively manufactured. In this latter regard, such medical appliances are normally shaped, e.g. by molding or extruding a thermoplastic material, which thermoplastic material, inherently, has the tensile properties required for the particular medical appliance. This means of manufacture is relatively inexpensive, as is required, and can be accurately controlled for size, shape, uniformity and reliability. Thus, any practical solution to the above problem must also include the ability for the medical appliance to be molded into the particular shape required by the medical appliance.
It would therefore be of substantial advantage to the art to provide a shapeable polymeric composition which is also bacteriocidal and which, in addition, has the required tensile properties for allowing formation thereof into practical and usual medical appliances of a relatively inexpensive nature.